Synergistic osteogenic and angiogenic effects of KP and QK peptides incorporated with an injectable and self-healing hydrogel for efficient bone regeneration

Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute. Therefore, the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity. However, the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved. Moreover, in order to achieve vascularized bone regeneration, alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost. In this study, a novel injectable self-healing hydrogel system (GMO hydrogel) loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect. The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities, which led to an excellent injectability and fittability. By photopolymerization of the enclosed GelMA, GMO hydrogel was further strengthened and thus more suitable for bone regeneration. Besides, the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction, leading to desired releasing profiles. In vitro, this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs. In vivo, KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria. Overall, the KP and QK loaded GMO hydrogel was injectable and self-healing, which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach.

Signaling pathways in obesity:mechanisms and therapeutic interventions

Obesity is a complex,chronic disease and global public health challenge.Characterized by excessive fat accumulation in the body,obesity sharply increases the risk of several diseases,such as type 2 diabetes,cardiovascular disease,and nonalcoholic fatty liver disease,and is linked to lower life expectancy.Although lifestyle intervention(diet and exercise)has remarkable effects on weight management,achieving long-term success at weight loss is extremely challenging,and the prevalence of obesity continues to rise worldwide.Over the past decades,the pathophysiology of obesity has been extensively investigated,and an increasing number of signal transduction pathways have been implicated in obesity,making it possible to fight obesity in a more effective and precise way.In this review,we summarize recent advances in the pathogenesis of obesity from both experimental and clinical studies,focusing on signaling pathways and their roles in the regulation of food intake,glucose homeostasis,adipogenesis,thermogenesis,and chronic inflammation.We also discuss the current antiobesity drugs,as well as weight loss compounds in clinical trials,that target these signals.The evolving knowledge of signaling transduction may shed light on the future direction of obesity research,as we move into a new era of precision medicine.

Outer delocalized electron aggregation of bromide bridged core–shell CuBr@C for hydrogen evolution reaction

Modulation of the surface electron distribution is a challenging problem that determines the adsorption ability of catalytic process.Here,we address this challenge by bridging the inner and outer layers of the core–shell structure through the bridge Br atom.Carbon shell wrapped copper bromide nanorods(CuBr@C)are constructed for the first time by chemical vapour deposition with hexabromobenzene(HBB).HBB pyrolysis provides both bridge Br atom and C shells.The C shell protects the stability of the internal halide structure,while the bridge Br atom triggers the rearrangement of the surface electrons and exhibits excellent electrocatalytic activity.Impressively,the hydrogen evolution reaction(HER)activity of CuBr@C is significantly better than that of commercial N-doped carbon nanotubes,surpassing commercial Pt/C at over 200 mA·cm^(−2).Density functional theory(DFT)calculations reveal that bridge Br atoms inspire aggregation of delocalized electrons on C-shell surfaces,leading to optimization of hydrogen adsorption energy.

Granulomatosis with polyangiitis presented as multiple cutaneous abscesses after hysterectomy

To the Editor:A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers[Figure 1A],occurring 1 month after a transvaginal hysterectomy due to uterine prolapse.Her general condition was good before and after the surgery,with no abnormal physical signs apart from metroptosis.She reported no fever,night sweat,cough,or abdominal pain,but 10 kg weight-loss.She has no history of diabetes,autoimmune diseases,or chronic infectious diseases.There was no similar illness in her family.

Regulation of TiO_(2) nanoarrays on titanium implants for enhanced osteogenic activity and immunomodulation

The surface topography of implants plays a major role in osteogenesis and immunomodulation.In this study,three types of TiO_(2) nanoarrays including nanorod arrays with a diameter of 45 nm(TiO_(2)-N),nanorod arrays with a diameter of 60 nm(TiO_(2)-N N),and nanocone arrays(TiO_(2)-NW)are prepared on titanium and the behavior of bone marrow stromal cells(BMSCs)and polarization of macrophages are studied.Compared to the planar titanium control,TiO_(2) nanoarrays facilitate osteogenesis of BMSCs and stimulate the pro-healing M2 phenotype.However,adhesion,spreading,proliferation,and osteogenic differentiation of BMSCs are more pronounced on TiO_(2)-N N than both TiO_(2)-N and TiO_(2)-NW.TiO_(2)-NN also produces the best immune microenvironment,while TiO_(2)-NW is more favorable than TiO_(2)-NN from the viewpoint of cell adhesion and spreading of osteoblasts.

Cyphellophora and its relatives in Phialophora: biodiversity and possible role in human infection

Cyphellophora is a genus of black yeast-like fungi characterised by having simple phialides with multiseptate,curved conidia.Judging from SSU and LSU data,Cyphellophora was found to be located in a well-supported clade within the Chaetothyriales comprising a number of species occurring on human skin and nail.Cyphellophora is phylogenetically close to Phialophora europaea,P.reptans and P.oxyspora,though morphologically these species produce singlecelled phialoconidia rather than multiseptate ones.Pseudomicrodochium suttonii and P.fusarioides have dark colonies and phylogenetically fit in with Cyphellophora;the type species of Pseudomicrodochium,P.aciculare,has similar,septate conidia but has a hyaline thallus.In the present study,multilocus phylogenetic analyses were combined with morphology and physiology.Sequences of the internal transcribed spacer region,the DNA dependent RNA polymerase II largest subunit and the partial beta tubulin gene were analysed for a set of 30 strains.Two novel species,Cyphellophora pauciseptata and Phialophora ambigua were discovered.Cyphellophora eucalypti was reduced to synonymy of C.guyanensis.The role of the studied fungi between colonization and infection of human skin was discussed.Putative virulence factors for these black yeast-like fungi were hypothesized to be the ability to assimilate monoaromatic hydrocarbons,to produce melanin pigments,and to tolerate the temperature of epidermal human skin.

Laboratory investigation of emulsified asphalt binder modified with wood-derived nano-cellulose and nano paper-cellulose

Emulsified asphalt is the primary material for preventive maintenance and cold-mix paving,but its low cohesive strength and poor mechanical properties limit its wide application,even with polymer modification.In this study,Styrene-Butadiene Rubber(SBR)emulsified asphalt was modified with nano-cellulose materials,namely nano paper-cellulose(NPC)and wood-derived nano-cellulose(WDC),to improve its properties.A novel preparation method of nano-cellulose solution was developed,including blending,ultrasonic stirring,and centrifugal treatment.Four types of nano-cellulose solution(0.5%NPC,0.5%,1.0%,and 1.5%WDC by weight of water)were selected.The microscopy analysis indicated that 0.5%WDC emulsion had a smaller particle size than 1.5%WDC emulsion.The rheology test indicated that WDC modified residue improved rutting resistance with the increased solution dosage due to the cross-linking effect,but its creep-and-recovery performance was worse than that of SBR emulsion residue.The NPC modified binder had a higher rutting factor than WDC modified binder at the same dosage after short-term aging.In addition,1.0%WDC could be regarded as the optimal dosage in terms of fatigue and low-temperature performance.Furthermore,Fourier Transform Infrared Spectroscopy(FTIR)results showed that 0.5%NPC modified residue performed better in long-term aging resistance compared with 0.5%WDC modified asphalt.

FPGA-based Digital Implementation of Flexible Power Control for Three-phase to Single-phase MMC-based Advanced Co-phase Traction Power Supply System

A three-phase to single-phase modular multilevel converter based advanced co-phase traction power supply(MMC-ACTPS) system is an effective structure to address the concerns of phase splitting and poor power quality of the conventional electrified railway. Due to the large number of MMCACTPS system modules, I/O resources and computing speed have high requirements on processors. Moreover, the module capacitor balance is challenging because the sorting time is too long when the traditional sorting algorithm for voltage balance is used. To solve the above issues, a digital implementation scheme of flexible power control strategy for three-phase to single-phase MMC-ACTPS system based on field programmable gate array(FPGA), which has sufficient I/O resources, has been proposed. Due to the parallel execution characteristics of the FPGA, the execution time of the controller and the modulator can be greatly reduced compared with a digital signal processor(DSP) + FPGA or DSpace. In addition, an improved sorting algorithm is proposed to reduce the sorting time and the implementation steps are analyzed. Finally, simulation and experimental results are presented to demonstrate the effectiveness and correctness of the proposed control strategy.

Updates in psoriasis diagnosis and treatment status in China:results from the National Psoriasis Center Registry

To the Editor:Psoriasis is a common chronic immunemediated systemic inflammatory disease[1]characterized by irritating skin erythema,reduced quality of life,and associated systemic diseases including cardiovascular disease,diabetes,and metabolic syndrome.In 2017,0.5%of China’s population was diagnosed with psoriasis.[2]To improve the overall diagnosis and treatment level of psoriasis in China,the National Clinical Research Center for Skin and Immune Disease launched a national collaborative project called the Psoriasis Standardized Diagnosis and Treatment Center(also named Psoriasis Center)project,[3]in which the first national real-world big data collection platform,Psoriasis Center Registry,was established with more than 300 medical centers across China by 2022.This study aimed to update the current general characteristics and treatment distribution of patients with psoriasis in China by describing the registry data at enrollment.